The systematic translation of cancer genomic data into knowledge of tumor biology and therapeutic avenues remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacologic annotation is available1. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number, and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacologic profiles for 24 anticancer drugs across 479 of the lines, this collection allowed identification of genetic, lineage, and gene expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Altogether, our results suggest that large, annotated cell line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of “personalized” therapeutic regimens2.

New, ultrasmall nanoparticles with sizes below 5 nm have been obtained. These small rigid platforms (SRP) are composed of a polysiloxane matrix with DOTAGA (1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid)-Gd(3+) chelates on their surface. They have been synthesised by an original top-down process: 1) formation of a gadolinium oxide Gd2O3 core, 2) encapsulation in a polysiloxane shell grafted with DOTAGA ligands, 3) dissolution of the gadolinium oxide core due to chelation of Gd(3+) by DOTAGA ligands and 4) polysiloxane fragmentation. These nanoparticles have been fully characterised using photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), a superconducting quantum interference device (SQUID) and electron paramagnetic resonance (EPR) to demonstrate the dissolution of the oxide core and by inductively coupled plasma mass spectrometry (ICP-MS), mass spectrometry, fluorescence spectroscopy, (29)Si solid-state NMR, (1)H NMR and diffusion ordered spectroscopy (DOSY) to determine the nanoparticle composition. Relaxivity measurements gave a longitudinal relaxivity r1 of 11.9 s(-1)  mM(-1) per Gd at 60 MHz. Finally, potentiometric titrations showed that Gd(3+) is strongly chelated to DOTAGA (complexation constant logβ110 =24.78) and cellular tests confirmed the that nanoconstructs had a very low toxicity. Moreover, SRPs are excreted from the body by renal clearance. Their efficiency as contrast agents for MRI has been proved and they are promising candidates as sensitising agents for image-guided radiotherapy.

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Magnetic resonance was used to investigate the kinetic disposition of magnetite nanoparticles (9.4 nm core diameter) from the blood circulation after intravenous injection of magnetite-based dextran-coated magnetic fluid in female Swiss mice. In the first 60 min the time-decay of the nanoparticle concentration in the blood circulation follows the one-exponential (one-compartment) model with a half-life of (6.9 +/- 0.7) min. The X-band spectra show a broad single line at g approximately 2, typical of nanomagnetic particles suspended in a nonmagnetic matrix. The resonance field shifts toward higher values as the particle concentration reduces, following two distinct regimes. At the higher concentration regime (above 10(14) cm(-3)) the particle-particle interaction responds for the nonlinear behavior, while at the lower concentration regime (below 10(14) cm(-3)) the particle-particle interaction is ruled out and the system recovers the linearity due to the demagnetizing field effect alone.

Electron paramagnetic resonance was used to investigate the magnetic material present in abdomens of Pachycondyla marginata ants. A g congruent with 4.3 resonance of high-spin ferric ions and a very narrow g congruent with 2 line are observed. Two principal resonance broad lines, one with g > 4.5 (LF) and the other in the region of g congruent with 2 (HF), were associated with the biomineralization process. The resonance field shift between these two lines, HF and LF, associated with magnetic nanoparticles indicates the presence of cluster structures containing on average three single units of magnetite-based nanoparticles. Analysis of the temperature dependence of the HF resonance linewidths supports the model picture of isolated magnetite nanostructures of approximately 13 nm in diameter with a magnetic energy of 544 K. These particles are shown to present a superparamagnetic behavior at room temperature. The use of these superparamagnetic particle properties for the magnetoreception process of the ants is suggested.

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In this study we present modifications in a phonon confinement model in order to obtain a better description for the Raman spectra of spherical nanocrystals, namely: bare-core, core–shell, and core–multishell. Our new interpretations allow investigating the influences of the interfacial alloying and strain effects on the vibrational spectra of core–shell nanocrystals. The robustness of the modified phonon confinement model was confirmed by precisely describing the Raman spectra of wurtzite CdSe/CdS core–shell magic-sized quantum dots (CS-MSQDs) synthesized directly in aqueous solution by a new route. The CdSe MSQD sample was used as template to growth CdSe/CdS CS-MSQDs with different shell thickness by setting the synthesis temperature. By using our modified model to fit the Raman spectra of samples, we have obtained the size dimensions of CS-MSQDs (core-diameter and shell-thickness), in excellent agreement with the values obtained by the atomic force microscopy results, confirming that the change in the synthesis temperature is a simple and efficient way to control the CdS-shell thickness during the growth process. Furthermore, we have confirmed the formation of an alloy layer (CdS x Se1‑x ) at the interface of these CdSe/CdS CS-MSQDs and that the strain effects can be neglected for the wurtzite structure.

Surface functionalization of a series of nanosized iron oxide particles (average diameter around 6 nm) with oleic acid was realized in this study. The aim is to suspend the surface-functionalized nanoparticulated materials in insulating mineral oil and evaluate their colloidal stability as a function of time. Nanoparticulated samples presenting stoichiometry close to maghemite were obtained by oxidation of a freshly precipitated magnetite sample. Systematic variations observed in the Fe3+/Fe2+ ratio, average particle size, and lattice constant were attributed to differences in oxidation route and oxidation condition employed. Morphological, compositional, thermal, optical and magnetic characterization techniques were used in the investigation of native (P, PN1, PN2, POX1, POX3, and POX7) and surface-functionalized (POA, PN1OA, PN2OA, POX1OA, POX3OA, and POX7OA) samples. While suspending the oleic-acid-coated nanosized iron oxide particles in insulating mineral oil, the best colloidal stability was achieved at the oxidation profile of Fe3+/Fe2+ = 40 (5.9 nm average core diameter), leading to a surface grafting coefficient of about 75% of a full monolayer coating of chemisorbed species only and resulting in the smallest observed hydrodynamic radius (8.1 nm). Within the range of our investigation, our findings reveal the characteristics and the chemical protocol used to produce a magnetic fluid sample embodying long-term colloidal stability, thus representing a very much promising material for application as a refrigerating fluid in power transformers and related devices.